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New Guidance Recommends Metformin to Prevent Antipsychotic Weight Gain
A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.
There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.
“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.”
The guideline was published online on December 9 in Schizophrenia Bulletin.
It offers three key recommendations:
- Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
- Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
- Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.
The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.
The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.
In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.
Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.
While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.
“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.
Experts Weigh In
This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.
Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”
While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.
Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.
“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.
Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.
“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.
“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.
Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.
Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.
This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.
There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.
“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.”
The guideline was published online on December 9 in Schizophrenia Bulletin.
It offers three key recommendations:
- Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
- Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
- Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.
The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.
The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.
In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.
Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.
While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.
“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.
Experts Weigh In
This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.
Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”
While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.
Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.
“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.
Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.
“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.
“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.
Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.
Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.
This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.
There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.
“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.”
The guideline was published online on December 9 in Schizophrenia Bulletin.
It offers three key recommendations:
- Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
- Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
- Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.
The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.
The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.
In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.
Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.
While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.
“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.
Experts Weigh In
This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.
Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”
While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.
Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.
“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.
Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.
“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.
“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.
Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.
Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.
This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
FROM SCHIZOPHRENIA BULLETIN
Most Effective Treatments for Adult ADHD Identified
, results of a large comprehensive meta-analysis showed.
The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.
Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.
“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.
The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.
The study was published online in The Lancet Psychiatry.
Bridging the Knowledge Gap
Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.
To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.
For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.
For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.
There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.
In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.
However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.
And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.
Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.
“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”
Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.
Experts Weigh In
Several experts weighed in on the results in a statement from the UK Science Media Center.
Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”
Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”
The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.
“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”
Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.
“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.
In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.
“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.
This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.
A version of this article first appeared on Medscape.com.
, results of a large comprehensive meta-analysis showed.
The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.
Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.
“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.
The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.
The study was published online in The Lancet Psychiatry.
Bridging the Knowledge Gap
Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.
To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.
For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.
For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.
There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.
In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.
However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.
And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.
Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.
“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”
Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.
Experts Weigh In
Several experts weighed in on the results in a statement from the UK Science Media Center.
Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”
Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”
The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.
“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”
Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.
“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.
In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.
“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.
This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.
A version of this article first appeared on Medscape.com.
, results of a large comprehensive meta-analysis showed.
The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.
Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.
“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.
The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.
The study was published online in The Lancet Psychiatry.
Bridging the Knowledge Gap
Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.
To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.
For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.
For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.
There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.
In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.
However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.
And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.
Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.
“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”
Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.
Experts Weigh In
Several experts weighed in on the results in a statement from the UK Science Media Center.
Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”
Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”
The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.
“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”
Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.
“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.
In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.
“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.
This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
APA Updates Guidance on Borderline Personality Disorder
For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).
The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.
“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas.
The updated guideline was published online in The American Journal of Psychiatry.
It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology.
Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty.
Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.
The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition.
The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment.
The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.
The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.
Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.
The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.
The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”
“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.
The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.
An Alternative Model of Care
Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults.
Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment.
The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning.
Oldham co-chaired the work group that developed the proposal for the alternative model.
“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said.
Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.
A version of this article first appeared on Medscape.com.
For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).
The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.
“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas.
The updated guideline was published online in The American Journal of Psychiatry.
It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology.
Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty.
Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.
The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition.
The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment.
The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.
The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.
Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.
The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.
The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”
“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.
The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.
An Alternative Model of Care
Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults.
Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment.
The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning.
Oldham co-chaired the work group that developed the proposal for the alternative model.
“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said.
Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.
A version of this article first appeared on Medscape.com.
For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).
The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.
“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas.
The updated guideline was published online in The American Journal of Psychiatry.
It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology.
Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty.
Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.
The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition.
The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment.
The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.
The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.
Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.
The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.
The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”
“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.
The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.
An Alternative Model of Care
Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults.
Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment.
The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning.
Oldham co-chaired the work group that developed the proposal for the alternative model.
“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said.
Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PSYCHIATRY
Do Risk-Reducing Surgeries Benefit BRCA Carriers With Early-Onset Breast Cancer History?
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SABCS 2024
New Cancer Drugs: Do Patients Prefer Faster Access or Clinical Benefit?
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
Does Acalabrutinib Fit Into Frontline MCL Therapy?
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
Rilzabrutinib Shines in Phase 3 Trial of Tough-to-Treat Immune Thrombocytopenia
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
Common Herbicide a Player in Neurodegeneration?
new research showed.
Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.
“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.
The study was published online in The Journal of Neuroinflammation.
Persistent Accumulation Within the Brain
Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.
The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”
In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain.
In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function.
In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.
They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period.
The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.
Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported.
Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted.
Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice.
Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival.
“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.
“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added.
Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
new research showed.
Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.
“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.
The study was published online in The Journal of Neuroinflammation.
Persistent Accumulation Within the Brain
Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.
The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”
In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain.
In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function.
In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.
They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period.
The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.
Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported.
Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted.
Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice.
Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival.
“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.
“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added.
Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
new research showed.
Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.
“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.
The study was published online in The Journal of Neuroinflammation.
Persistent Accumulation Within the Brain
Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.
The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”
In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain.
In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function.
In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.
They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period.
The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.
Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported.
Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted.
Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice.
Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival.
“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.
“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added.
Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF NEUROINFLAMMATION
CRC Screening Uptake Rises in Adults Aged 45-49 Years
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
NCCN Expands Cancer Genetic Risk Assessment Guidelines
Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.
For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.
“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.
Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.
The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants.
For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.”
“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release.
“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.
A version of this article first appeared on Medscape.com.
Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.
For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.
“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.
Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.
The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants.
For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.”
“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release.
“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.
A version of this article first appeared on Medscape.com.
Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.
For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.
“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.
Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.
The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants.
For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.”
“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release.
“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.
A version of this article first appeared on Medscape.com.